Omega-3 Fatty Acids: Studies Don't Support Heart Benefit

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A systematic review and meta-analysis was designed to summarize evidence about the associations between fatty acid consumption and coronary disease in light of nutritional guidelines which generally encourage low consumption of saturated fats and high consumption of omega-3 polyunsaturated fatty acids from fish or plant sources.

The review found that current evidence does not clearly support guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.

Dietary guidelines that encourage high intake of polyunsaturated fatty acids and low consumption of saturated fats are not clearly supported by research, according to a recent meta-analysis.

When data from 27 randomized controlled trials of fatty acid supplementation was analyzed, the relative risks for coronary disease were 0.97 (95% CI 0.69 to 1.36) with beta-linolenic acid, 0.94 (95% CI 0.86 to 1.03) for long-chain omega-3 polyunsaturated acid, and 0.89 (95% CI 0.71 to 1.12) for omega-6 polyunsaturated fatty acid, Rajiv Chowdhury, MD, PhD, of the University of Cambridge, and his co-authors wrote March 17 in the Annals of Internal Medicine.

Analysis of 32 observational studies found that the relative risks for coronary disease, comparing top and the bottom third of baseline dietary fatty acid intake, were 1.01 (95% CI 0.97 to 1.07) for saturated, 0.99 (95% CI 0.89 to 1.09) for monounsaturated, 0.93 (95% CI 0.84 to 1.02) for long-chain omega-3 polyunsaturated, 1.01 (95% CI 0.96 to 1.07) for omega-6 polyunsaturated, and 1.16 (95% CI 1.06 to 1.27) for trans fatty acids.

"The pattern of this analysis did not yield clearly supportive evidence for current cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of saturated fats," concluded Chowdhury and his co-authors. What's more, they said, "Nutritional guidelines on fatty acids and cardiovascular guidelines may require reappraisal to reflect the current evidence."

The meta-analysis included more than 600,000 participants from 18 countries. All of the studies were published before July 1, 2013. The majority were culled from electronic searches of Medline, Science Citation Index, and the Cochrane Central Register of Controlled Trials. The researchers also looked for relevant studies in the reference lists of identified articles, and for author correspondence related to the studies.

The review "provides a comprehensive systematic synthesis of available evidence," the authors said.

Nutritional guidelines have encouraged low intake of saturated fats, high consumption of omega-3 polyunsaturated fatty acids from fish and plant sources, and avoidance of trans fats, especially partially hydrogenated fat, as a way to improve cardiovascular health, the authors wrote.

But there has been considerable variation, they said, in the international guidelines about the amount and types of fatty acids. "This variation reflects, in part, uncertainties in the available evidence," they authors said.

Interpretation of prospective observational studies has been complicated by potential misclassification in the self-report questionnaires, they said. Early analyses also did not assess the consistency between dietary self-report and biomarker measures of fatty acids in coronary disease, they noted.

Additionally, interpretation of randomized trials of fatty acid supplements has been complicated by the difference in dietary habits of trial populations, the absence, presence, and type of vascular disease in study populations at the beginning of trials, trial duration, composition of supplement regimens, and differences in the efficacy of coronary prevention, the authors said.

Earlier this year, James DiNicolantonio, PharmD, a cardiovascular research scientist at Saint Luke's Mid America Heart Institute in Kansas City, Mo., wrote an editorial in BMJ's Open Heart journal questioning the evidence for guidelines, calling the benefits of a low-fat diet -- especially a diet that replaces saturated fats with carbohydrates or omega-6 polyunsaturated fatty acids -- "severely challenged."

Previous meta-analyses "inappropriately combined trials that were mixed omega-3 and omega-6 and stated that they were omega-6 trials," he said, in an email to MedPage Today. "When looking at the trials that solely replaced saturated fat with omega-6, there was an increase in CHD [coronary heart disease] and CV [cardiovascular] death."

Past meta-analyses also inappropriately excluded the Sydney Diet Heart Study and another study investigating the consumption of corn oil patients with a history of heart disease, both of which showed harm when omega-6 replaced saturated fat, said DiNicolantonio, who believes the high-carb, low-fat diet many followed as a result of the current guidelines has contributed to the obesity epidemic and the rise in diabetes and metabolic syndrome.

Studies like this one should lead to the public eating "real" food, "even if these foods contain high amounts of saturated fat, instead of ingesting industrialized seed oils, particularly corn and safflower oil," says DiNicolantonio.

The authors of this meta-analysis acknowledged limitations to their study. These included a "moderate" amount of available data on some circulating fatty acids and "possible overestimation of associations because of preferential publications of extreme findings or selective reporting of results for particular fatty acids with striking associations," the authors said.

Selective reporting appeared minimal in the randomized trials, they said. But they noted that few observational studies reported on all measured circulating fatty acids. "Therefore it is possible that selective under-reporting may have contributed at least in part to the observational findings in this meta-analysis."

This study was supported by the British Heart Foundation, Medical Research Council, Cambridge National Institute for Health Research Biomedical Research Centre, and Gates Cambridge.

Co-authors disclosed relevant relationships with a number of companies and institutions, including Nestle, Metagenics, Pfizer, Merck Sharp & Dohme, Novartis, Roche Pharmaceuticals, the Medical Research Council, the British Heart Foundation, Cancer Research UK, Quaker Oats, AstraZeneca, UpToDate, GlaxoSmithKline, Merck, the National Heart, Lung and Blood Institute, the National Institute of Neurological Disorders, the Wellcome Trust, and Elsevier (France).

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

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